This proposal describes six projects which focus on the anatomy, physiology, and neurochemistry of the efferent system, with two projects in each of these areas. Four of the six projects focus further on questions concerning efferent development. In the first of the six projects, our work on the origins and terminations of the olivocochlear bundle in adult animals will be extended to studies of postnatal development and to studies of the ultrastructure of the efferent innervation of the organ of Corti. In the second project, we will explore issues concerning the comparative anatomy of the efferent system at various stages of embryonic and postnatal development. The use of chickens and frogs as well as mice will allow experimental manipulation of developing systems. In the third project, we will measure the electrophysiological properties of efferent fibers in the internal auditory canal and determine the consequences of efferent stimulation on afferent responses in developing animals. In the fourth project, we will continue our work on measurement of cochlear function in humans, focusing on the relation between physiological and otoacoustic- emission measures of efferent and afferent function in both infants and adults. In the fifth project, we will apply established electrophysiological and neurochemical techniques to a unique preparation consisting of isolated efferent nerve terminals. In the sixth and final project, we will continue work on the cholinergic properties of the efferent system, using the neurotoxin AF64 and other approaches.